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RAF proteins exert both specific and compensatory functions during tumor progression of NRAS driven melanoma.

Dorard, Coralie ; Estrada, Charlène LU ; Barbotin, Céline ; Larcher, Magalie ; Garancher, Alexandra ; Leloup, Jessy ; Beermann, Friedrich ; Baccarini, Manuela ; Pouponnot, Celio and Larue, Lionel , et al. (2017) In Nature Communications 8.
Abstract
NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally,... (More)
NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally, proliferation of resistant cells emerging in the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation. These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven melanoma. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
8
article number
15262
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85019238659
ISSN
2041-1723
DOI
10.1038/ncomms15262
language
English
LU publication?
no
id
c340ab1f-8c92-40a8-94cf-5cccc3718049
date added to LUP
2022-03-28 14:06:46
date last changed
2022-03-29 04:27:18
@article{c340ab1f-8c92-40a8-94cf-5cccc3718049,
  abstract     = {{NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally, proliferation of resistant cells emerging in the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation. These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven melanoma.}},
  author       = {{Dorard, Coralie and Estrada, Charlène and Barbotin, Céline and Larcher, Magalie and Garancher, Alexandra and Leloup, Jessy and Beermann, Friedrich and Baccarini, Manuela and Pouponnot, Celio and Larue, Lionel and Alain Eychène, Alain and Druillennec, Sabine}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{RAF proteins exert both specific and compensatory functions during tumor progression of NRAS driven melanoma.}},
  url          = {{http://dx.doi.org/10.1038/ncomms15262}},
  doi          = {{10.1038/ncomms15262}},
  volume       = {{8}},
  year         = {{2017}},
}